Striatal Blood-Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study.
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
02
05
2022
received:
17
02
2022
accepted:
01
06
2022
pubmed:
30
6
2022
medline:
19
10
2022
entrez:
29
6
2022
Statut:
ppublish
Résumé
Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD. Here, we report a prospective, single-arm, nonrandomized, proof-of-concept, phase I clinical trial (NCT03608553 amended) in PD with dementia to test the safety and feasibility of striatal BBB opening in PD patients. Seven PD patients with cognitive impairment were treated for BBB opening in the posterior putamen. This was performed in two sessions separated by 2 to 4 weeks, where the second session included bilateral putamina opening in 3 patients. Primary outcome measures included safety and feasibility of focal striatal BBB opening. Changes in motor and cognitive functions, magnetic resonance imaging (MRI), The procedure was feasible and well tolerated, with no serious adverse events. No neurologically relevant change in motor and cognitive (battery of neuropsychological tests) functions was recognized at follow-up. MRI revealed putamen BBB closing shortly after treatment (24 hours to 14 days) and ruled out hemorrhagic and ischemic lesions. There was a discrete but significant reduction in β-amyloid uptake in the targeted region and no change in FDOPA PET. These initial results indicate that FUS-mediated striatal BBB opening is feasible and safe and therefore could become an effective tool to facilitate the delivery of putative neurorestorative molecules in PD. © 2022 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD.
OBJECTIVE
Here, we report a prospective, single-arm, nonrandomized, proof-of-concept, phase I clinical trial (NCT03608553 amended) in PD with dementia to test the safety and feasibility of striatal BBB opening in PD patients.
METHODS
Seven PD patients with cognitive impairment were treated for BBB opening in the posterior putamen. This was performed in two sessions separated by 2 to 4 weeks, where the second session included bilateral putamina opening in 3 patients. Primary outcome measures included safety and feasibility of focal striatal BBB opening. Changes in motor and cognitive functions, magnetic resonance imaging (MRI),
RESULTS
The procedure was feasible and well tolerated, with no serious adverse events. No neurologically relevant change in motor and cognitive (battery of neuropsychological tests) functions was recognized at follow-up. MRI revealed putamen BBB closing shortly after treatment (24 hours to 14 days) and ruled out hemorrhagic and ischemic lesions. There was a discrete but significant reduction in β-amyloid uptake in the targeted region and no change in FDOPA PET.
CONCLUSIONS
These initial results indicate that FUS-mediated striatal BBB opening is feasible and safe and therefore could become an effective tool to facilitate the delivery of putative neurorestorative molecules in PD. © 2022 International Parkinson and Movement Disorder Society.
Substances chimiques
Amyloid beta-Peptides
0
fluorodopa F 18
2C598205QX
Dihydroxyphenylalanine
63-84-3
Banques de données
ClinicalTrials.gov
['NCT03608553']
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2057-2065Informations de copyright
© 2022 International Parkinson and Movement Disorder Society.
Références
CSF PWM. Blood-brain barrier, and brain drug delivery [internet]. Expert Opin Drug Deliv 2016;13(7):963-975.
Lipsman N, Meng Y, Bethune AJ, et al. Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound. Nat Commun 2018;9(1):1-8.
Park SH, Baik K, Jeon S, et al. Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer's disease: a proof-of-concept study [internet]. Transl Neurodegener 2021;10(1):1-11.
Rezai AR, Ranjan M, D'Haese PF, et al. Noninvasive hippocampal blood−brain barrier opening in Alzheimer's disease with focused ultrasound. Proc Natl Acad Sci USA 2020;117(17):9180-9182.
Abrahao A, Meng Y, Llinas M, et al. First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound [internet]. Nat Commun 2019;10(1):1-9.
Gasca-salas C, Fernández-rodríguez B, Pineda-pardo JA, et al. Blood-brain barrier opening with focused ultrasound in Parkinson's disease dementia [internet]. Nat. Commun 2021;12(1):1-7.
Bhatia KP, Marsden CD. The behavioural and motor consequences of focal lesions of the basal ganglia in man. Brain 1994;117(4):859-876.
D'Haese PF, Ranjan M, Song A, et al. β-Amyloid plaque reduction in the hippocampus after focused ultrasound-induced blood-brain barrier opening in Alzheimer's disease. Front Hum Neurosci 2020;14(October):1-5.
Burgess A, Dubey S, Yeung S, et al. Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior [internet]. Radiology 2014;273(3):736-745.
Leinenga G, Gotz J. Scanning ultrasound removes amyloid- and restores memory in an Alzheimer's disease mouse model [internet]. Sci. Transl. Med 2015;7(278):278ra33
Jordão JF, Ayala-Grosso CA, Markham K, et al. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the TgCRND8 mouse model of Alzheimer's disease. PLoS One 2010;5(5):4-11.
Nisbet RM, Van Der Jeugd A, Leinenga G, et al. Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model. Brain 2017;140(5):1220-1230.
Kalaitzakis ME, Walls AJ, Pearce RKB, Gentleman SM. Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes [internet]. Neurobiol Dis 2011;41(2):377-384.
Fiorenzato E, Biundo R, Cecchin D, et al. Brain amyloid contribution to cognitive dysfunction in early-stage Parkinson's disease: the PPMI dataset. J Alzheimers Dis 2018;66(1):229-237.
Foster ER, Campbell MC, Burack MA, et al. Amyloid imaging of Lewy body-associated disorders. Mov Disord 2010;25(15):2516-2523.
Tustison NJ, Avants BB, Cook PA, et al. N4ITK: improved N3 bias correction. IEEE Trans Med Imaging 2010;29(6):1310-1320.
Coupe P, Yger P, Prima S, et al. An optimized blockwise nonlocal means denoising filter for 3-D magnetic resonance images. IEEE Trans Med Imaging 2008;27(4):425-441.
Smith SM. Fast robust automated brain extraction. [internet]. Hum. Brain Mapp 2002;17(3):143-155.
Avants BB, Epstein CL, Grossman M, Gee JC. Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal 2008;12(1):26-41.
Baschi R, Luca A, Nicoletti A, et al. Changes in motor, cognitive, and behavioral symptoms in Parkinson's disease and mild cognitive impairment during the COVID-19 lockdown. Front Psych 2020;11(590134):1-10.
Palermo G, Tommasini L, Baldacci F, et al. Impact of coronavirus disease 2019 pandemic on cognition in Parkinson's disease. Mov Disord 2020;35(10):1717-1718.
Karakatsani ME, Blesa J, Konofagou EE. Blood-brain barrier opening with focused ultrasound in experimental models of Parkinson's disease. Mov Disord 2019;34(9):1252-1261.
Xhima K, Markham-Coultes K, Hahn Kofoed R, et al. Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies. Brain 2021 Dec 17;awab460
Ismail II, Kamel WA, Al-Hashel JY. Association of COVID-19 pandemic and rate of cognitive decline in patients with dementia and mild cognitive impairment: a cross-sectional study. Gerontol Geriatr Med 2021;7:23337214211005224
Torboli D, Mioni G, Bussé C, et al. Subjective experience of time in dementia with Lewy bodies during COVID-19 lockdown. Curr Psychol 2021 May 8;1-10.
Talbot CV, Briggs P. “Getting back to normality seems as big of a step as going into lockdown”: the impact of the COVID-19 pandemic on people with early to middle stage dementia. Age Ageing 2021;50(3):657-663.
Barguilla A, Fernández-Lebrero A, Estragués-Gázquez I, et al. Effects of COVID-19 pandemic confinement in patients with cognitive impairment. Front Neurol 2020;11(589901):1-8.
Tsapanou A, Zoi P, Kalligerou F, et al. The effect of prolonged lockdown due to COVID-19 on Greek demented patients of different stages and on their caregivers. J Alzheimers Dis 2021;83(2):907-913.
Park SH, Kim MJ, Jung HH, et al. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J Neurosurg 2020;134:475-483.
Poewe W, Wenning GK. The natural history of Parkinson's disease. J Neurol 2006;253(Suppl 7:VII):2-6.
Monje MHG, Sánchez-Ferro A, Pineda-Pardo JA, et al. Motor onset topography and progression in Parkinson's disease: the upper limb is first. Mov Disord 2021;36(4):905-915.
Pineda-Pardo JA, Sánchez-Ferro A, Monje MHG, Obeso JA. Onset pattern of nigrostriatal denervation in early Parkinson's disease. Brain 2022;145:1018-1028.
Blesa J, Foffani G, Dehay B, et al. Motor and non-motor circuit disturbances in early Parkinson disease: which happens first? Nat Rev Neurosci 2021;23(2):115-128.